Mechanistic insights into elastin degradation by pseudolysin, the major virulence factor of the opportunistic pathogen Pseudomonas aeruginosa.
Mechanistic insights into elastin degradation by pseudolysin, the major virulence factor of the opportunistic pathogen Pseudomonas aeruginosa.
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机会性病原体铜绿假单胞菌的主要毒力因子假溶血素降解弹性蛋白的机制见解
DOI：
10.1038/srep09936
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发表时间：
2015-04-23
影响因子：
4.6
通讯作者：
Zhang YZ
中科院分区：
文献类型：
--
作者：
Yang J;Zhao HL;Ran LY;Li CY;Zhang XY;Su HN;Shi M;Zhou BC;Chen XL;Zhang YZ
假溶血素是铜绿假单胞菌分泌的最丰富的蛋白酶，是这种机会性人类病原体的主要细胞外毒力因子。假溶素通过溶解弹性蛋白破坏人体组织。然而，假溶素结合和降解弹性蛋白的机制仍然难以捉摸。在本研究中，我们通过生化实验、显微观察和定点诱变研究了假溶素对弹性蛋白结合和降解的作用机制。假溶素与牛弹性蛋白纤维结合，并倾向于攻击弹性蛋白疏水结构域P1和P1 '位置的疏水残基肽键。在显微镜下进一步研究了假溶血素对牛弹性蛋白纤维和交联人弹力蛋白的降解过程。综上所述，研究结果表明，假溶素对弹性蛋白的降解始于纤维表面的疏水结构域，随后是宏观弹性蛋白纤维逐渐分解为主要结构元件。此外，我们的位点导向突变结果表明，S1-S1亚位点上的五个疏水残基在假溶素与弹性蛋白的结合中发挥了关键作用。本研究揭示了p的发病机制。aeruginosainfection。
Pseudolysin is the most abundant protease secreted byPseudomonas aeruginosaand is the major extracellular virulence factor of this opportunistic human pathogen. Pseudolysin destroys human tissues by solubilizing elastin. However, the mechanisms by which pseudolysin binds to and degrades elastin remain elusive. In this study, we investigated the mechanism of action of pseudolysin on elastin binding and degradation by biochemical assay, microscopy and site-directed mutagenesis. Pseudolysin bound to bovine elastin fibers and preferred to attack peptide bonds with hydrophobic residues at the P1 and P1’ positions in the hydrophobic domains of elastin. The time-course degradation processes of both bovine elastin fibers and cross-linked human tropoelastin by pseudolysin were further investigated by microscopy. Altogether, the results indicate that elastin degradation by pseudolysin began with the hydrophobic domains on the fiber surface, followed by the progressive disassembly of macroscopic elastin fibers into primary structural elements. Moreover, our site-directed mutational results indicate that five hydrophobic residues in the S1-S1’ sub-sites played key roles in the binding of pseudolysin to elastin. This study sheds lights on the pathogenesis ofP. aeruginosainfection.
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影响因子：
4.8
作者：
Wang, Yu-Kai;Zhao, Guo-Yan;Zhang, Yu-Zhong
通讯作者：
Zhang, Yu-Zhong
DOI：
10.1016/j.bbrc.2012.04.157
发表时间：
2012-06-01
影响因子：
3.1
作者：
Carson, Louise;Cathcart, George R.;Gilmore, Brendan F.
通讯作者：
Gilmore, Brendan F.
DOI：
10.1073/pnas.1014280108
发表时间：
2011-03-15
影响因子：
11.1
作者：
Baldock, Clair;Oberhauser, Andres F.;Weiss, Anthony S.
通讯作者：
Weiss, Anthony S.
影响因子：
4.8
作者：
Xie, Bin-Bin;Bian, Fei;Zhang, Yu-Zhong
通讯作者：
Zhang, Yu-Zhong
影响因子：
2.4
作者：
Yu, J;Peter, C;Urban, JPG
通讯作者：
Urban, JPG